A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Followed by an Active-Treatment Extension to Evaluate the Efficacy and Safety of Apremilast(CC-10004) in the Treatment of Behçet Disease

Number of Oral Ulcers at Day 85 [ Time Frame: Day 85 ] [ Designated as safety issue: No ]

The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline).

Secondary Outcome Measures:

Pain of Oral Ulcers as Measured by Visual Analog Scale (VAS) at Day 85 [ Time Frame: Day 85 ] [ Designated as safety issue: No ]

A 100-mm VAS pain scale for oral ulcers was completed by the participant at timepoints specified in the protocol. Each 100-mm VAS was presented to the participant on a single sheet of bond paper. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded. When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.

Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) Scores at Day 85 [ Time Frame: Baseline to Day 85 ] [ Designated as safety issue: No ]

A 100-mm VAS pain scale for genital ulcers was completed by the participant at timepoints specified in the protocol. Each 100-mm VAS was presented to the participant on a single sheet of bond paper. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded. When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.

Area Under the Curve (AUC) for the Number of Oral Ulcers From Day 1 to 85 [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]

Area under curve (AUC^85) from Day 1 to Day 85 for the number of oral ulcers per day was determined using the trapezoidal rule and divided by the days between the date of the last observation and baseline. The AUC was determined using the LOCF approach to impute missing values.

Area Under the Curve for the Number of Genital Ulcers From Day 1 to 85 [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]

Area under curve (AUC^85) from Day 1 to Day 85 for the number of genital ulcers per day was not analyzed.

Area Under the Curve (AUC) for the Number of Oral Plus Genital Ulcers From Day 1 to 85 [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]

Area under curve (AUC) from Day 1 to Day 85 (AUC^85) for the number of oral plus genital ulcers per day was determined using the trapezoidal rule and divided by the days between the date of the last observation and baseline. The AUC was determined using the LOCF approach to impute missing values.

Sum of the Number Oral Ulcers, Genital Ulcers or Oral Plus Genital Ulcers at Day 85 [ Time Frame: Day 85 ] [ Designated as safety issue: No ]

Sum of the number oral ulcers, genital ulcers or oral plus genital ulcers at Day 85

Percentage of Participants Who Were Oral Ulcer-free (Complete Response), or Whose Oral Ulcers Were Reduced by ≥ 50%, (Partial Response) [ Time Frame: Baseline and Day 85 ] [ Designated as safety issue: No ]

Comparison of the percentage of participants who were oral ulcer-free (complete response: free from active oral ulcers), or whose oral ulcers were reduced by ≥ 50%, (partial response) between the apremilast-treated and the placebo-treated groups. In this case, partial response also includes complete response.

Change From Baseline in the Disease Activity as Measured by BD Current Activity Form/Index Score on Day 85 [ Time Frame: Day 1 to Day 85 or to early termination visit ] [ Designated as safety issue: No ]

The Behçet's Disease Current Activity Index consists of three component scores, a participant's perception of disease activity, a clinician's overall perception of disease activity and a Behçet's Disease Current Activity Index Score. The score ranges from 0 to 12. A higher score indicates higher level of disease activity (worsening) and a negative change from baseline indicates improvement.

Number of Treatment Emergent Adverse Events (TEAE) During the Placebo Controlled Treatment Phase [ Time Frame: Day 1 to Day 85; maximum exposure to study drug was 13 weeks during treatment phase ] [ Designated as safety issue: Yes ]

A Treatment Emergent Adverse Event (TEAE) was defined as any AE occurring or worsening on or after the first treatment of any study drug, and within 28 days after the last dose of the last study drug. A treatment related toxicity was considered by the investigator to be not suspected or suspected. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE.

Number of New Manifestations of Behçet's Disease or Flare During the Placebo Controlled Treatment Phase [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: Yes ]

A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:

Oral/genital ulcers: ≥ 100% increase in the number of oral or genital ulcers from Day 1 or a minimum increase of 3 in the number of oral or genital ulcers, whichever is greater;

Arthritis: ≥ 50% increase in the number of swollen joints, or a minimum increase of 3 swollen joints, whichever is greater;

Skin lesions (non-oral/genital ulcers): ≥ 50% increase in the total score of the Physician's Global Assessment of Skin Lesions, or a minimum increase of 2 in the total score of the Physician's Global Assessment of Skin Lesions, whichever is greater'

Number of Oral Ulcers at Day 169 [ Time Frame: Day 169 ] [ Designated as safety issue: No ]

The number of oral ulcers were counted at Day 169 in reference to the participants' first day of active treatment (Day 1 or Day 85).

Pain of Oral Ulcers as Measured by VAS (VAS Score) at Day 169 [ Time Frame: Day 169 ] [ Designated as safety issue: No ]

A 100-mm VAS pain scale for oral ulcers was completed by the participant at timepoints specified in the protocol. Each 100-mm VAS was presented to the participant on a single sheet of bond paper. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded. When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.

Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) at Day 169 [ Time Frame: Day 1 to Day 169 ] [ Designated as safety issue: No ]

A 100-mm VAS pain scale for genital ulcers was completed by the participant at timepoints specified in the protocol. Each 100-mm VAS was presented to the participant on a single sheet of bond paper. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded. When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.

Behçet's Disease (BD) Current Activity Index Form Score at Day 169 [ Time Frame: Day 169 ] [ Designated as safety issue: No ]

The Behçet's Disease Current Activity Index consists of three component scores, a participant's perception of disease activity, a clinician's overall perception of disease activity and a Behçet's Disease Current Activity Index Score. The score ranges from 0 to 12. A higher score indicates higher level of disease activity (worsening) and a negative change from baseline indicates improvement.

Number of New Manifestations of Behçet's Disease or Flare That Were Not Present at Day 1 [ Time Frame: Day 1 to Day 169 ] [ Designated as safety issue: Yes ]

A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:

Oral/genital ulcers: ≥ 100% increase in the number of oral or genital ulcers from Day 1 or a minimum increase of 3 in the number of oral or genital ulcers, whichever is greater;

Arthritis: ≥ 50% increase in the number of swollen joints, or a minimum increase of 3 swollen joints, whichever is greater;

Skin lesions (non-oral/genital ulcers): ≥ 50% increase in the total score of the Physician's Global Assessment of Skin Lesions, or a minimum increase of 2 in the total score of the Physician's Global Assessment of Skin Lesions, whichever is greater;

Number of Oral Ulcers at Day 197 [ Time Frame: Day 197 ] [ Designated as safety issue: No ]

The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline).

Pain of Oral Ulcers as Measured by VAS (VAS Score) at Day 197 [ Time Frame: Day 197 ] [ Designated as safety issue: No ]

A 100-mm VAS pain scale for oral ulcers was completed by the participant at timepoints specified in the protocol. Each 100-mm VAS was presented to the participant on a single sheet of bond paper. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded. When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.

Pain of Genital Ulcers as Measured by Visual Analog Scale (VAS) at Day 197 [ Time Frame: Day 1 to Day 197 ] [ Designated as safety issue: No ]

A 100-mm VAS pain scale for genital ulcers was completed by the participant at timepoints specified in the protocol. Each 100-mm VAS was presented to the participant on a single sheet of bond paper. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded. When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points.

Change From Baseline in the Disease Activity as Measured by BD Current Activity Form/Index Score on Day 197 [ Time Frame: Day 1 to Day 197 ] [ Designated as safety issue: No ]

The Behçet's Disease Current Activity Index consists of three component scores, a participant's perception of disease activity, a clinician's overall perception of disease activity and a Behçet's Disease Current Activity Index Score. The score ranges from 0 to 12. A higher score indicates higher level of disease activity (worsening) and a negative change from baseline indicates improvement.

A Treatment Emergent Adverse Event (TEAE) is as any AE occurring or worsening on or after the first treatment of any study drug, and within 28 days after the last dose of the last study drug. A treatment related toxicity was considered by the investigator to be not suspected or suspected. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE.

Other Outcome Measures:

Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 85 [ Time Frame: Baseline to Day 85 ] [ Designated as safety issue: No ]

The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)

Percentage of Participants Who Were Genital Ulcer-free (Complete Response) at Day 169 [ Time Frame: Day 1 to Day 169 ] [ Designated as safety issue: No ]

The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)

Percentage of Participants Who Were Genital Ulcer-free (Complete Response) [ Time Frame: Day 1 to Day 197 ] [ Designated as safety issue: No ]

The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers)

History of malignancy (except for treated basal-cell skin carcinomas > 3 years prior to screening)

Any active major organ involvement of Behçet Disease

Use of concomitant immune modulating therapy or topical corticosteroids.

Use of ocular corticosteroids

Use of any investigational medication within 4 weeks prior to randomization or 5 Pharmacokinetic/Pharmacodynamic (PK/PD) half-lives (whichever is longer)

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00866359